Immune-checkpoint inhibitor (ICI)–related diarrhea is attributed to inflammatory colitis, with no other drug-related differential diagnosis. Here, we investigated the occurrence of pancreatic atrophy (PA) in ICI-treated cancer patients and its correlation to exocrine pancreatic insufficiency (EPI). Metastatic melanoma, non–small cell lung carcinoma, and head and neck squamous cell carcinoma patients (n ¼ 403) treated with anti–PD-1 (n ¼ 356) or anti–CTLA-4 (n ¼ 47) were divided into a case group (radiologic evidence of PA); control group matched by age, gender, and previous lines of treatment; and colitis group (ICI-induced colitis). Quantitative pancreatic volumetry was used for calculation of the decrease in pancreatic volume over time (atrophy rate). Thirty-one patients (7.7%) developed PA compared with 41 matched controls (P ¼ 0.006). Four patients developed EPI, all from the anti–PD-1–treated group, which resolved with oral enzyme supplementation. The atrophy rate did not correlate with EPI (P ¼ 0.87). EPI-related diarrhea presented at a median of 9 months, whereas the diarrhea of anti–PD-1–induced colitis patients (n ¼ 22) was presented at a median of 2 months (P ¼ 0.029). ICI-induced PA is irreversible and can result in EPI. EPI should be suspected in cases of late-onset steroid-resistant diarrhea with features of steatorrhea and treated with oral enzyme supplements.
Bibliographical noteFunding Information:
G. Markel was supported by The Saban Family Team Science Award and Israel Ministry of Economy Grant 60958. E.N. Baruch was supported by the Allen Berg Fund for Excellence in Immuno-Oncology Research, Young Researcher Scholarship. The authors would like to thank Haya and Nehemia Lemelbaum for their generous and continuous support. The authors would also like to thank patients and their families. This work is part of the PhD thesis of E.N. Baruch.
G. Markel was supported by The Saban Family Team Science Award and Israel Ministry of Economy Grant 60958. E.N. Baruch was supported by the Allen Berg Fund for Excellence in Immuno-Oncology Research, Young Researcher Scholarship.
©2018 American Association for Cancer Research.